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Targeting modulation of the choroid plexus blood-CSF barrier and CSF hypersecretion via lipid nanoparticle-mediated co-delivery of siRNA and resveratrol

Author

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  • Qiguang Wang

    (Sichuan University)

  • Xue Xia

    (Sichuan University)

  • Huan Zhang

    (Sichuan University)

  • Yue Li

    (Sichuan University)

  • Lei Zhu

    (Sichuan University)

  • Yulong Shi

    (Sichuan University)

  • Yuzhao Tang

    (Sichuan University)

  • Jian Cheng

    (Sichuan University)

  • Xuhui Hui

    (Sichuan University)

  • Huile Gao

    (Sichuan University)

Abstract

Hydrocephalus is one of the most common neurological disorders, but pharmacotherapy options are currently lacking due to the complex pathogenesis. The blood-CSF barrier (BCSFB), consisting of choroid plexus (ChP) epithelial cells, is a crucial gate for the entry of peripheral immune cells and its dysfunction emerges as an important contributor to hydrocephalus pathology. Meanwhile, SPAK-mediated CSF hypersecretion in ChP epithelial cells plays an important role in hydrocephalus. Here, we fabricated a transferrin receptor-targeted nano-drug (siR/RSV@TNP) that can intelligently navigate to the blood-CSF barrier and prepared for combined delivery of resveratrol (RSV) and SPAK siRNA (siSPAK) for synergetic hydrocephalus therapy. As expected, siR/RSV@TNP fulfilled its function of knocking down SPAK expression, relieving inflammation and oxidative stress, retrieving blood-CSF barrier integrity, and ultimately preventing ventriculomegaly and hydrocephalus in male mice. Here, we demonstrate that targeting the choroid plexus blood-CSF barrier and cerebrospinal fluid hypersecretion offers a promising approach for alleviating hydrocephalus.

Suggested Citation

  • Qiguang Wang & Xue Xia & Huan Zhang & Yue Li & Lei Zhu & Yulong Shi & Yuzhao Tang & Jian Cheng & Xuhui Hui & Huile Gao, 2025. "Targeting modulation of the choroid plexus blood-CSF barrier and CSF hypersecretion via lipid nanoparticle-mediated co-delivery of siRNA and resveratrol," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61543-1
    DOI: 10.1038/s41467-025-61543-1
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    1. Jinwei Zhang & Mohammad Iqbal H. Bhuiyan & Ting Zhang & Jason K. Karimy & Zhijuan Wu & Victoria M. Fiesler & Jingfang Zhang & Huachen Huang & Md Nabiul Hasan & Anna E. Skrzypiec & Mariusz Mucha & Dani, 2020. "Modulation of brain cation-Cl− cotransport via the SPAK kinase inhibitor ZT-1a," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Michael J. Boivin & Angelina M. Kakooza & Benjamin C. Warf & Leslie L. Davidson & Elena L. Grigorenko, 2015. "Reducing neurodevelopmental disorders and disability through research and interventions," Nature, Nature, vol. 527(7578), pages 155-160, November.
    3. Annette B. Steffensen & Eva K. Oernbo & Anca Stoica & Niklas J. Gerkau & Dagne Barbuskaite & Katerina Tritsaris & Christine R. Rose & Nanna MacAulay, 2018. "Cotransporter-mediated water transport underlying cerebrospinal fluid formation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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